School of Life Sciences, Gwangju Institute of Science and Technology (GIST), Gwangju, Republic of Korea.
School of Biotechnology, Jawaharlal Nehru University, New Delhi, India; Centre for Bioinformatics, Computational and Systems Biology, Pathfinder Research and Training Foundation, Greater Noida, India.
Infect Genet Evol. 2022 Apr;99:105254. doi: 10.1016/j.meegid.2022.105254. Epub 2022 Feb 23.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), accountable for causing the coronavirus diseases 2019 (COVID-19), is already declared as a pandemic disease globally. Like previously reported SARS-CoV strain, the novel SARS-CoV-2 also initiates the viral pathogenesis via docking viral spike-protein with the membranal angiotensin-converting enzyme 2 (ACE2) - a receptor on variety of cells in the human body. Therefore, COVID-19 is broadly characterized as a disease that targets multiple organs, particularly causing acute complications via organ-specific pathogenesis accompanied by destruction of ACE2 cells, including alveolus, cardiac microvasculature, endothelium, and glomerulus. Under such circumstances, the high expression of ACE2 in predisposing individuals associated with anomalous production of the renin-angiotensin system (RAS) may promote enhanced viral load in COVID-19, which comparatively triggers excessive apoptosis. Furthermore, multi-organ injuries were found linked to altered ACE2 expression and inequality between the ACE2/angiotensin-(1-7)/mitochondrial Ang system (MAS) and renin-angiotensin-system (RAS) in COVID-19 patients. However, the exact pathogenesis of multi-organ damage in COVID-19 is still obscure, but several perspectives have been postulated, involving altered ACE2 expression linked with direct/indirect damages by the virus-induced immune responses, such as cytokinin storm. Thus, insights into the invasion of a virus with respect to ACE2 expression site can be helpful to simulate or understand the possible complications in the targeted organ during viral infection. Hence, this review summarizes the multiple organs invasion by SARS CoV-2 linked with ACE2 expression and their consequences, which can be helpful in the management of the COVID-19 pathogenesis under life-threatening conditions.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）是导致 2019 年冠状病毒病（COVID-19）的病原体，现已在全球范围内被宣布为大流行疾病。与之前报道的 SARS-CoV 株一样，新型 SARS-CoV-2 也是通过病毒刺突蛋白与细胞膜血管紧张素转换酶 2（ACE2）-人体各种细胞上的一种受体结合来引发病毒发病机制。因此，COVID-19 广泛表现为一种多器官疾病，特别是通过特定器官发病机制导致 ACE2 细胞破坏，包括肺泡、心脏微血管、内皮细胞和肾小球，从而导致急性并发症。在这种情况下，与肾素血管紧张素系统（RAS）异常产生相关的易感个体中 ACE2 的高表达可能会促进 COVID-19 中病毒载量的增加，从而导致过度细胞凋亡。此外，在 COVID-19 患者中发现多器官损伤与 ACE2 表达改变以及 ACE2/血管紧张素-(1-7)/线粒体 Ang 系统（MAS）与肾素血管紧张素系统（RAS）之间的不平衡有关。然而，COVID-19 中多器官损伤的确切发病机制仍不清楚，但已经提出了几种观点，涉及与病毒诱导的免疫反应（如细胞因子风暴）直接/间接损伤相关的 ACE2 表达改变。因此，深入了解病毒对 ACE2 表达部位的入侵有助于模拟或理解病毒感染期间靶向器官可能发生的并发症。因此，本综述总结了 SARS-CoV-2 与 ACE2 表达相关的多个器官入侵及其后果，这有助于在危及生命的情况下管理 COVID-19 发病机制。
